Enhanced in vitro anticancer activity of a platinum-Mesalazine complex against colorectal cancer cells apoptotic modulation and evidence of non-intercalative DNA binding.

Colorectal cancer (CRC) remains a major global health burden, while current therapeutic strategies are often constrained by limited efficacy and adverse side effects. This study evaluated the anticancer activity and DNA-binding properties of a novel platinum-Mesalazine complex (Pt-MES) compared with Mesalazine (MES) in human CRC cells. Cytotoxicity was assessed using the MTT assay, gene expression was analyzed by qPCR, and drug-DNA interactions were investigated through viscosimetry, UV-visible spectroscopy, and molecular docking. Both compounds exhibited dose-dependent cytotoxicity; however, Pt-MES demonstrated superior antiproliferative activity, with a lower IC₅₀ value (2.694 µg/mL) than MES (3.503 µg/mL), indicating enhanced efficacy following platinum complexation. Gene expression analysis revealed that Pt-MES promoted apoptosis by upregulating FASLG, BAX, and miRNA-122, while suppressing Bcl-2, telomerase, and miRNA-21. In contrast, MES exerted weaker regulatory effects on these molecular targets. Biophysical studies showed a slight reduction in DNA viscosity accompanied by hyperchromic shifts in UV-visible spectra, suggesting a predominantly non-intercalative mode of DNA interaction. Molecular docking further supported preferential binding within the DNA minor groove. These findings indicate that Pt-MES may interact with DNA grooves and facilitate platinum coordination with nucleophilic sites, particularly guanine residues, leading to DNA structural perturbation and activation of apoptotic pathways. In addition, Pt-MES may influence key pathways implicated in CRC progression, including NF-κB, Wnt/β-catenin, and COX-2 signaling. Collectively, the results demonstrate that Pt-MES exhibits enhanced in vitro anticancer activity relative to MES and represents a promising multi-targeted candidate for further preclinical investigation in colorectal cancer.